PMID- 28388001
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20190816
IS  - 1747-0285 (Electronic)
IS  - 1747-0277 (Linking)
VI  - 90
IP  - 5
DP  - 2017 Nov
TI  - Exploring the RNA-bound and RNA-free human Argonaute-2 by molecular dynamics 
      simulation method.
PG  - 753-763
LID - 10.1111/cbdd.12997 [doi]
AB  - Argonaute 2 (Ago2) protein is the major vehicle of microRNAs (miRNAs)-guided gene 
      repression and silencing processes. Although the crystal structure of human Ago2 
      (hAgo2) has recently been disclosed, the information of dynamically structural 
      character of protein-RNA recognition is still lacking. Molecular dynamics 
      simulations were used to systematically explore hAgo2 in the presence and absence 
      of RNA duplex. Stable direct and water-mediated hydrogen bonds were observed 
      between guide RNA backbone atoms and hAgo2, especially for nucleotides 2-7. In 
      addition, water-mediated hydrogen bonds are indicated to be critical in the 
      specific recognition between hAgo2 and the conserved adenine in position 1 of 
      target RNA. The core domains (N, PAZ, MID, and PIWI) possess rigid body movements 
      during the simulations. The motions of N-PAZ and PIWI-MID are negatively 
      correlated with or without RNA binding and PAZ domain is identified as the most 
      mobile domain in both systems. The reorientation of PAZ domain not only 
      influences the binding of helix-7 and RNA duplex, the initial pairing process, 
      but also the shape of N-PAZ cleft, where the supplemental base pairing occurs. It 
      is speculated that PAZ domain could be a key regulator in hAgo2-mediated 
      miRNA-induced gene regulation.
CI  - (c) 2017 John Wiley & Sons A/S.
FAU - Kong, Ren
AU  - Kong R
AUID- ORCID: 0000-0001-9010-1750
AD  - School of Electrical and Information Engineering, Institute of Bioinformatics and 
      Medical Engineering, Jiangsu University of Technology, Changzhou, China.
FAU - Xu, Lei
AU  - Xu L
AD  - School of Electrical and Information Engineering, Institute of Bioinformatics and 
      Medical Engineering, Jiangsu University of Technology, Changzhou, China.
FAU - Piao, Lianhua
AU  - Piao L
AD  - School of Electrical and Information Engineering, Institute of Bioinformatics and 
      Medical Engineering, Jiangsu University of Technology, Changzhou, China.
FAU - Zhang, Dawei
AU  - Zhang D
AD  - School of Electrical and Information Engineering, Institute of Bioinformatics and 
      Medical Engineering, Jiangsu University of Technology, Changzhou, China.
FAU - Hou, Ting-Jun
AU  - Hou TJ
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
FAU - Chang, Shan
AU  - Chang S
AD  - School of Electrical and Information Engineering, Institute of Bioinformatics and 
      Medical Engineering, Jiangsu University of Technology, Changzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20170512
PL  - England
TA  - Chem Biol Drug Des
JT  - Chemical biology & drug design
JID - 101262549
RN  - 0 (AGO2 protein, human)
RN  - 0 (Argonaute Proteins)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Argonaute Proteins/chemistry/*metabolism
MH  - Binding Sites
MH  - Humans
MH  - Hydrogen Bonding
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Protein Binding
MH  - Protein Domains
MH  - RNA/*metabolism
OTO - NOTNLM
OT  - RNA silencing
OT  - conformational changes
OT  - human Argonaute 2
OT  - molecular dynamics simulation
EDAT- 2017/04/08 06:00
MHDA- 2017/11/14 06:00
CRDT- 2017/04/08 06:00
PHST- 2017/02/11 00:00 [received]
PHST- 2017/03/22 00:00 [revised]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
PHST- 2017/04/08 06:00 [entrez]
AID - 10.1111/cbdd.12997 [doi]
PST - ppublish
SO  - Chem Biol Drug Des. 2017 Nov;90(5):753-763. doi: 10.1111/cbdd.12997. Epub 2017 
      May 12.